A Phase I/II Study to Determine the Maximum Tolerated Dose (MTD) and Safety of CC-4047 (Pomalidomide) Administered in Conjunction With Cisplatin and Etoposide

The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 21-day cycle of treatment. The MTD Phase included the Treatment period (Cycle 1: Identification of the MTD) and the Extension period (Cycles 2 to 6: Confirmation of Safety of the MTD). (See Secondary Outcome Measure 2 for data on DLTs.)

Time frame: Cycle 1 (21 days)

Population: Safety Population

Duration of Response was calculated from first Partial Response (PR) or Complete Response (CR) to disease progression. Duration of response was censored at the last date that the participant was known to be progression-free for: 1) participants who had not progressed at the time of analysis; 2) participants who had been removed from the treatment phase prior to documentation of progression.

Time frame: From first Partial Response (PR) or Complete Response (CR) to disease progression (maximum of 19.4 weeks)

Population: Number of participants in ITT population who were considered Responders.

For the purposes of determining the MTD (see Primary Outcome Measure), a DLT was defined as any 1 or more of the following: inability to deliver all 3 doses of cisplatin and etoposide due to toxicity; inability to deliver 14 consecutive days of daily pomalidomide dosing because the participant did not tolerate the medication due to any of the following: ≥ grade 3 non-hematological toxicity (excluding alopecia) occurring before Day 14 of pomalidomide dosing; febrile neutropenia (absolute neutrophil count \[ANC\] \<1,000/µL and fever \>101ºF, core temperature); grade 4 neutropenia of ≥7 days duration with onset on or before Day 14 of pomalidomide dosing; platelet count \<25,000/µL occurring before Day 14 of pomalidomide dosing. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 4.0, grades: 1=mild, 2=moderate, 3=severe, 4=life threatening, 5=death.

Time frame: Cycles 1 - 6 (21-day cycles)

Population: Safety Population

Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute \[NCI\] Common Toxicity Criteria for Adverse Events \[CTCAE\], Version 4.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.

Time frame: Cycles 1-6 (21-day cycles). Median (full range) duration of exposure (in weeks) to pomalidomide (MTD Phase): 1 mg, 17.9 (1.0, 20.3); 3 mg, 17.0 (16.9, 22.0); 4 mg, 14.0 (0.7, 22.0); 5 mg, 13.0 (2.0, 22.1). Cisplatin and etoposide: 15.3 (0.4, 20.6).

Population: Safety population

Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. TEAE = any AE occurring or worsening on or after the first treatment with any study drug. 'Related' = suspected by investigator to be related to study treatment. National Cancer Institute \[NCI\] Common Toxicity Criteria for Adverse Events \[CTCAE\], Version 4.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.

Time frame: Cycle 7 to discontinuation (21-day cycles). Median (full range) duration of exposure (in weeks) to pomalidomide during Maintenance Phase was 5.0 (1.1, 36.0).

Population: Safety population; participants continuing in the Recovery Period and Maintenance Phase.

Overall Survival was defined as time (in weeks) from enrollment to death. The median is based on Kaplan-Meier estimate, with 95% confidence intervals about the median overall survival. Overall survival was censored at the last time participant was known to be alive for those who were alive at time of analysis.

Time frame: From enrollment through study termination (approximately 35 months)

Population: Participants in the ITT population.

Investigator's best assessment of response based on RECIST criteria during the MTD phase. For target lesions: Complete Response (CR)=Disappearance of all target lesions; Partial Response (PR)=≥30% decrease in sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD; Progressed Disease (PD)=≥20% increase in sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or the appearance of ≥1 new lesions; Stable Disease (SD)=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since treatment started. For non-target lesions: CR= Disappearance of all non-target lesions and normalization of tumor marker level; Incomplete Response/SD=Persistence of ≥1 non-target lesions and/or maintenance of tumor marker level above normal limits; PD=Appearance of ≥1 new lesions; unequivocal progression of existing non-target lesions.

Time frame: Cycles 1 -6 (21-day cycles)

Population: ITT population. 'Not Assessed' category includes participants who did not have adequate data for response assessment at baseline and/or post-baseline prior to the use of any non-protocol anti-tumor therapy.